This application represents the renewal of the UCLA National Neurological AIDS Bank (NNAB) for an additional 5 years of funding to carry out the resource and research activities of the Bank. Since 1998, NNAB has provided human tissues, fluids, and data for research into the causes and treatment of Neuro-AIDS. NNAB has recruited a racially, ethnically, and linguistically diverse cohort distinctive to and representative of the greater Los Angeles, CA area. We have successfully conducted a longitudinal study of persons with advanced AIDS and HIV-seronegative controls. These subjects have agreed to undergo serial clinical examinations, to donate their blood, urine, and cerebrospinal fluid during their lives, and to donate their tissues and organs after their deaths. A group of subjects also receives separately funded longitudinal magnetic resonance imaging/magnetic resonance spectroscopy scans that add further scientific value to the cohort. Between 2002 and mid-2007 we filled 68 unique requests comprised of tissue and fluids to AIDS researchers worldwide. NNAB also collects information about co-morbid conditions that interact with HIV in the pathogenesis of neurological and psychiatric disorders, and investigates the best methods to detect cognitive impairment in our HIV+ minority subjects. Herein, we describe our new research agenda. We have taken the lead in plans for NNTC co-morbidity research, that will increase the value of the NNTC samples by adding data on aging, hepatitis, metabolic and cardiovascular disorders, tobacco use, adherence, use of non-HIV medications, and by enriching the substance abuse data collected. We have recruited 2 new members to the Scientific Leadership Group who offer expertise in epidemiology and Neuro-AIDS clinical studies. We have developed studies to better diagnose neurocognitive disorders in our diverse cohort, to search for host-genetic markers of AIDS-related neurological and psychiatric disorders, and we have increased our collaborations with investigators who study neurovirology, genetics, toxicity of HIV drugs, and substance abuse. NNAB offers an invaluable resource and research asset to the scientific community and to people afflicted by Neuro-AIDS. Lay Language Summary: The NNAB study recruits and examines donors with AIDS and other diseases. Volunteers agree to donate medical information and samples of their body fluids during their lives, and their tissues and organs after their deaths. This tissue is distributed to worthy scientists for the purpose of medical research. NNAB also conducts its own research into the diagnosis, causes, and cures for neurological diseases associated with HIV infection, such as HIV dementia, myelopathy, peripheral neuropathy, myopathy, psychiatric disorders, and medication toxicity in HIV patients. Part A: